The metabolism and pharmacokinetics of carcinogens in pregnant, fetal, and infant mice are correlated with tumor incidence. Suckling Swiss mice were treated with dimethylnitrosamine (DMN). Liver and lung tumors resulted. Pretreatment of the mothers of these mice with Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs), resulted in transmammary exposure of the sucklings and had several interesting effects on DMN-caused tumorigenesis. The PCBs provided significant protection against initiation of liver and lung tumors. Induction in the sucklings of an enzyme effecting detoxification of DMN was demonstrated and was postulated to be the mechanism of the observed protection. A second effect of the PCBs was a significant increase in the percent mice with livers overgrown by tumor, a phenomenon which was thought to be due to liver tumor promotion by the PCBs. Thus the interaction of maternally-derived PCBs with DMN tumorigenesis was complex, giving protection against tumor initiation but also stimulating tumor growth. The effect of vehicle and diet on rate of absorption of 14C-DMN from the stomachs of adult and suckling mice has been investigated, since this rate detemines both length of time of exposure of the gastric mucosa and pharmacokinetics of carcinogen contact with distal target organs. Ethanol or oil retarded DMN loss from the stomachs of both adults and sucklings, and the nature of maternal diet may have influenced rate of gastric DMN departure in fed sucklings. A study of effect of diet and vehicle on oral DMN tumorigenesis in infant mice is planned. In an investigation in progress, the metabolism and pharmacokinetics of methylcholanthrene (MC) in maternal, fetal, and placental tissues are measured and correlated with incidence of tumors induced transplacentally by MC. Genetic backcrosses of C57BL/6 mice, which are highly inducible for the enzyme metabolizing MC, and DBA/2 mice which are noninducible, are used as the pharmacogenetic model, providing both inducible and noninducible fetuses in mothers that are either inducible or noninducible.